Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus, particularly the HIV-1 strain. Most currently approved therapies for HIV infection target the viral reverse transcriptase and protease enzymes, with additional approved drugs targeting the viral integrase enzyme and the viral gp41 protein, to inhibit viral entry. Within the reverse transcriptase inhibitor and protease inhibitor classes, resistance of HIV to existing drugs is a problem. Therefore, it is important to discover and develop new antiretroviral compounds.
Oral dosing is the most common and convenient route of drug administration. It is well recognized that intestinal permeability is an important factor controlling the bioavailability (absorption) of orally administered drugs to enter the general circulation in order to reach the site of action for the compound to exert its effect. The in vitro Caco-2 permeability assay is a system commonly used to model and predict the intestinal permeability of a compound. Studies have demonstrated that compounds with low Caco-2 permeability display low oral bioavailability in humans and other pre-clinical species. By contrast, compounds with high Caco-2 permeability display higher levels of bioavailability in humans and other pre-clinical species (Zheng Yang et. al., Journal of Pharmaceutical Science, 2010, Vol 99, No. 4, 2135-2152).
WO 2010/115264 describes compounds that are useful in the treatment of HIV infection.